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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An X-linked clone encoding exons 4-9 of the hypoxanthine phosphoribosyltransferase (HPRT) gene was isolated from a kangaroo (Macropus robustus: Marsupialia) lambda EMBL4 genomic library. Sequence similarity between the kangaroo and eutherian HPRT coding sequences was high; however, intron sizes varied significantly between the kangaroo and other eutherian species. HpaII and HhaI sites in the body of the gene were generally hypermethylated in vivo on the active, relative to the inactive X, with sites within intron 3 showing essentially complete correspondence of activity with methylation and inactivity with unmethylation. At approximately 5 kb downstream from the gene, a switch to unmethylation of active X-linked sites occurred. This switch occurred within a cluster of HpaII and HhaI sites that may represent a CG island associated with a subsequent gene.
Somat Cell Mol Genet 1993 Mar
PMID:Isolation of a clone partially encoding hill kangaroo X-linked hypoxanthine phosphoribosyltransferase: sex differences in methylation in the body of the gene. 768 49

ABP-280 is a ubiquitous actin binding protein present in the cytoskeleton of many different cell types. ABP-280 was mapped to distal Xq28, 50-60 kb downstream of the Green Colour Pigment (GCP) genes. To establish if ABP-280 may be a candidate for one of the muscle disease localized by linkage analysis to distal Xq28 we looked for alternative forms of ABP-280 mRNA. Several different ABP-280 mRNAs were indeed identified: two are X-linked and are produced by alternative splicing of a small exon of 24 nucleotides. At least one additional gene encoding a RNA more than 70% identical to ABP-280 in the 1700 bp sequenced has also been found. It was mapped to chromosome 7. While both forms of the X-linked ABP-280 are ubiquitous, the gene on chromosome 7 is highly expressed only in skeletal muscle and heart. The two genes were therefore excellent candidates for the X-linked and for the autosomal dominant form of the Emery-Dreifuss Muscular Dystrophy (EDMD) both of which have been described. So far, however we were unable to demonstrate mutations in the coding region or affecting the alternative splicing of the X-linked form of ABP-280, in several patients studied, and we think that it is quite unlikely that this is the gene responsible for EDMD.
Hum Mol Genet 1993 Jun
PMID:Mapping of two genes encoding isoforms of the actin binding protein ABP-280, a dystrophin like protein, to Xq28 and to chromosome 7. 768 10

Orofacial clefting is genetically complex, no single gene being responsible for all forms. It can, however, result from a single gene defect either as part of a syndrome (e.g. van der Woude syndrome, Treacher-Collins syndrome, velo-cardio-facial syndrome) or as an isolated phenotypic effect (e.g. X-linked cleft palate; non-syndromic, autosomal dominant orofacial clefting). Several studies have suggested that chromosome 6p is a candidate region for a locus involved in orofacial clefting. We have used YAC clones from contigs in 6p25-p23 to investigate three unrelated cases of cleft lip and palate coincident with chromosome 6p abnormalities. Case 1 has bilateral cleft lip and palate and a balanced translocation reported as 46,XY,t(6,7)(p23;q36.1). Case 2 has multiple abnormalities including cleft lip and palate and was reported as 46,XX,del(6)(p23;pter). Case 3 has bilateral cleft lip and palate and carries a balanced translocation reported as 46,XX,t(6;9)(p23;q22.3). We have identified two YAC clones, both of which cross the breakpoint in cases 1 and 3 and are deleted in case 2. These clones map to 6p24.3 and therefore suggest the presence of a locus for orofacial clefting in this region. The HGP22 and AP2 genes, potentially involved in face formation, have been found to flank this region, while F13A maps further telomeric in 6p24.3/25.
Hum Mol Genet 1995 Jan
PMID:Evidence of a locus for orofacial clefting on human chromosome 6p24 and STS content map of the region. 771 23

Phosphorylase kinase (PHK) is a key enzyme in the control of glycogen breakdown. Several types of PHK deficiency have been described of which X-linked liver glycogenosis type I (XLG I) is the most common. Since the XLG I locus and the gene encoding the liver alpha-subunit gene of PHK (PHKA2) have both been localized to Xp22, PHKA2 was a candidate gene for XLG I. In this study we identified four point mutations in four unrelated XLG I patients: three mutations introduce a premature stop codon, whereas the fourth mutation abolishes a splice site consensus sequence leading to exon skipping. These findings indicate that PHKA2 is the XLG I gene.
Hum Mol Genet 1995 Jan
PMID:Mutations in the phosphorylase kinase gene PHKA2 are responsible for X-linked liver glycogen storage disease. 771 37

Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation process, has been reported to be associated with Alport syndrome (AS), a familial nephropathy, mainly dominant X-linked inherited, and characterized by ultrastructural changes of the glomerular basement membrane. The COL4A5 gene, encoding the alpha 5 chain of type IV collagen, has been identified as the site of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen chain encoding gene has been mapped closely upstream of COL4A5, and disruption of the 5' end of both genes has been reported in four patients with DL and AS (DL-AS). Here, we report a long-range restriction map around the COL4A6 locus, and show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS encompasses only the two first exons of COL4A6, with a breakpoint located in the second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate that three patients with AS without DL, known to have a deletion of the 5' part of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA product was detected by reverse-transcription-polymerase chain reaction in an oesophageal tumour sample of a patient with DL-AS. These results suggest that DL-AS could be caused by an abnormal truncated alpha 6(IV) chain.
Hum Mol Genet 1995 Jan
PMID:Deletions of both alpha 5(IV) and alpha 6(IV) collagen genes in Alport syndrome and in Alport syndrome associated with smooth muscle tumours. 771 41

Using sequence data from the last introns of ZFX and ZFY genes, we previously estimated the male-to-female ratio (alpha) of mutation rate to be close to 6 in higher primates and 1.8 in rodents. As the mutation rate may vary among different regions of the mammalian genome, it is interesting to see whether sequence data from other regions will give similar estimates. In this study, we have determined the partial genomic sequences of the ubiquitin-activating enzyme E1 genes (Ube 1x and Ube 1y for the X-linked and Y-linked homologues, respectively) of mice and rats and two mouse Ube 1y pseudogenes. From the intron sequences of the Ube 1 genes, we calculated the divergence of the Y-linked genes (Y = 0.161) and that of the X-linked genes (X = 0.107) between mouse and rat, and found the Y/X ratio to be 1.50. This ratio led to an estimate of alpha = 2.0 with a 95% confidence interval of (1.0, 3.9). Similar estimates of alpha were obtained if mouse Ube 1y pseudogenes were used instead of the mouse Ube 1y functional gene. These estimates are consistent with our previous estimate for rodents and suggest that the sex ratio of mutation rate in rodents is approximately only one-third of that in higher primates. Our estimate of the divergence time between Ube 1x and Ube 1y supports the view that the two genes separated before the eutherian radiation.
J Mol Evol 1995 Jan
PMID:Estimating the intensity of male-driven evolution in rodents by using X-linked and Y-linked Ube 1 genes and pseudogenes. 771 13

The mouse homolog of the human DXS423E (SB1.8) gene has been isolated by screening a mouse cDNA library. Like its human counterpart, the mouse Sb1.8 gene is X-linked, as shown by Southern blot analysis and by in situ hybridization to metaphase chromosomes. Sb1.8 was sublocalized to band F of the mouse X chromosome, distal to Alas2 and proximal to DXPas1, which confirms a region of conservation between band Xp11.21-p11.22 in human and band XF in mouse. In situ hybridization also showed that the Smcx (Xe169) gene maps near Sb1.8 in band F. The Sb1.8 gene was shown to be highly conserved in mammals; partial DNA sequence analysis indicates 92% identity between the mouse and human genes. In contrast to the human DXS423E gene, the mouse Sb1.8 gene is subject to X inactivation, as shown by restriction enzyme and sequence analysis of mRNA from mice with Searle's translocation (T(X;16)16H). Absence of Sb1.8 expression from the inactive mouse X chromosome in vitro was confirmed by analysis of a cell line (Hobmski) in which the M. spretus X chromosome is inactivated. The Sb1.8 gene is a new member of a group of genes that escape X inactivation in human, but are inactivated in mouse.
Hum Mol Genet 1995 Feb
PMID:The mouse Sb1.8 gene located at the distal end of the X chromosome is subject to X inactivation. 775 76

Microsatellites are widely recognised as providing a rich source of polymorphic markers for genetic mapping. Consequently, highly polymorphic CA repeats tightly linked to a disease locus are invaluable tools in linkage studies. We have developed an efficient technique for cloning microsatellite repeats from a region of interest contained within a yeast artificial chromosome (YAC). The YAC material is digested with a frequent cutting restriction endonuclease and ligated to polymerase chain reaction (PCR) amplifiable catch-linkers. A 5' biotinylated (CA)11 oligonucleotide is then used to select fragments containing a complementary repeat by binding to streptavidin-coated magnetic beads. The catch-linkers enable these fragments to be PCR amplified, cloned and sequenced. Primers are then designed to amplify the repeat locus and to confirm its genomic localization and heterozygosity. We have successfully used this technique to clone a new (CA)18 microsatellite from a 360-kb YAC. The YAC contains the CYBB locus in Xp21.1 and is thought to contain at least part of the RP3 gene responsible for X-linked retinitis pigmentosa. This new CA repeat is highly polymorphic with nine alleles identified so far and a heterozygosity of 0.75.
Mol Cell Probes 1995 Feb
PMID:A simple method for rapid isolation of microsatellites from yeast artificial chromosomes. 776 Aug 61

The contribution of induced mutations to the burden of genetic disease in the context of population genetics is considered. A clear distinction is made between the effects of genetic disease and mutational events. Much of the existing burden of genetic disease is a consequence of mutations that occurred in the past. The problem of distinguishing between spontaneous and induced mutations is discussed. Molecular genetics techniques are blurring the definitions of these terms. Classical population genetics shows that the frequency of affected individuals will reach an equilibrium depending on the mutation rate and the selective pressure against affected individuals. Increasing the mutation rate or reducing the selective pressures would result in a new equilibrium with an increase in the frequency in subsequent generations of affected individuals with dominant and X-linked mutant alleles. The increase in the number of recessive mutant alleles would be much slower and take many generations to reach the new equilibrium level. One assumption behind such equilibria is random mating. Changes in human demography with a rapid increase in population size, the breakup of small, relatively inbred subpopulations, and relaxed selective pressures will lead to a new equilibrium for recessive genes at probably higher frequencies. These factors will be the major contributors to increasing the burden of recessive genetic disease by increasing the total numbers of cases. The proportion of the population with a genetic disease will also continue to grow as a greater proportion of the population survives to late middle age and succumbs to diseases associated with old age, such as cancer, circulatory disease, dementias, and diabetes, each of which is likely to have a genetic component.(ABSTRACT TRUNCATED AT 250 WORDS)
Environ Mol Mutagen 1995
PMID:Population genetics of induced mutations. 778 63

We have sequenced the entire exon (approximately 1.180 bp) encoding the zinc finger domain of the X-linked and Y-linked zinc finger genes (ZFX and ZFY, respectively) in the orangutan, the baboon, the squirrel monkey, and the rat; a total of 9,442 bp were sequenced. The ratio of the rates of synonymous substitution in the ZFY and ZFX genes is estimated to be 2.1 in primates. This is close to the ratio of 2.3 estimated from primate ZFY and ZFX intron sequences and supports the view that the male-to-female ratio of mutation rate in humans in considerably higher than 1 but not extremely large. The ratio of synonymous substitution rates in ZFY and ZFX is estimated to be 1.3 in the rat lineage but 4.2 in the mouse lineage. The former is close to the estimate (1.4) from introns. The much higher ratio in the mouse lineage (not statistically significant) might have arisen from relaxation of selective constraints. The synonymous divergence between mouse and rat ZFX is considerably lower than that between mouse and rat autosomal genes, agreeing with previous observations and providing some evidence for stronger selective constraints on synonymous changes in X-linked genes than in autosomal genes. At the protein level ZFX has been highly conserved in all placental mammals studied while ZFY has been well conserved in primates and foxes but has evolved rapidly in mice and rats, possibly due to relaxation of functional constraints as a result of the development of X-inactivation of ZFX in rodents. The long persistence of the ZFY-ZFX gene pair in mammals provides some insight into the process of degeneration of Y-linked genes.
J Mol Evol 1994 Dec
PMID:Contrasting rates of nucleotide substitution in the X-linked and Y-linked zinc finger genes. 780 46


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